A broadly applicable, stress-mediated bacterial death pathway regulated by the phosphotransferase system (PTS) and the cAMP-Crp cascade

Significance Finding that pan-tolerance derives from defects in carbohydrate regulation connects stress-mediated lesions with metabolic change, identifies a stable type of tolerance, and demonstrates a widely shared death response. Manipulation of the response should improve antimicrobial efficacy, preserve beneficial bacteria during antimicrobial use, and protect industrial bacteria from toxic products. Mutations in many genes can interfere with stress-mediated metabolism; thus, mutation to pan-tolerance could be a high-probability event. Finding that selection of tolerance to one lethal stressor confers tolerance to many, if not all, indicates that massive disinfectant consumption potentially undermines antimicrobial efficacy and immune defenses against pathogenic bacteria. Since pan-tolerance is hidden from current surveillance of resistance, the work indicates a need for facile methods to measure tolerance.